GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE

人的发展是个体生物化学的总和 过程，每一个基因编程功能，在一个系统的 的方式，导致酶的最终表达和定位 或蛋白质。 酶的开发和定位 需要几个基因，这些基因的功能是处理，时间， 结构、靶向和受体基因作用于结构 基因产物 遗传性溶酶体酶疾病相关 异常发育提供了很好的模型， 研究不同数量和类型的基因所需的 酶的发展。 这项研究旨在解剖， 确定和表征几个新的基因所必需的， 最终形成溶酶体酶。 为了实现这一点，2 将研究几组溶酶体酶疾病： 粘脂沉积症和芳基硫酸酯酶A缺乏症。 每个 涉及几个受影响的基因，所有这些基因都是 溶酶体酶的发育。 粘脂沉积症（ML） 由MLII和MLIII组成，其特征在于高尔基体GlcNAc-P- 转移酶（GNPT）缺乏影响生物合成， 溶酶体酶的定位。 我们已经确定了至少3个 需要的基因。 芳基硫酸酯酶-A缺乏症 包括异染性脑白质营养不良， 缺乏症，假性缺乏症，和 激活剂缺乏症 芳基硫酸酯酶-A也缺乏， 粘脂增多症 我们的证据表明至少有10个基因 参与芳基硫酸酯酶-A（ARSA）的最终表达。 因此，本研究具有解剖和 鉴定至少10个参与加工的新基因， 一般而言，溶酶体酶的靶向和开发，以及 尤其是ARSA。 体细胞研究将从基因上解剖和识别 基因. 遗传学、生物化学、免疫学和分子生物学 提出了对基因和酶进行表征的研究。 大家族已确定为粘脂沉积症基因连锁 问题研究 我们的证据表明有几种类型的基因，包括 结构、加工、靶向、时间和受体。 克隆 基因将被用来表征GNPT组织，疾病- 相关突变体和基因表达。 所有标记均已显影 将可用于遗传咨询，人口筛查， 基因定位和诊断。 这些研究将描述涉及 在溶酶体酶的表达、加工和靶向中， 这将为人类发展提供基本信息， 以及遗传学和溶酶体的生物合成。

Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.